Apparatus and methods for sealing a vascular puncture

ABSTRACT

Apparatus for sealing a puncture communicating with a blood vessel includes a porous carrier formed from lyophilized hydrogel or other material. The plug may include at least first and second hydrogel precursors and a pH adjusting agent carried by the porous carrier in an unreactive state prior to exposure to an aqueous physiological environment. Once exposed to bodily fluids, the carrier expands as the lyophilized material hydrates to enhance and facilitate rapid hemostasis of the puncture. When the plug is placed into the puncture, the natural wetting of the plug by bodily fluids (e.g., blood) causes the first and second precursors to react and cross-link into an adhesive or “sticky” hydrogel that aids in retaining the plug in place within the puncture.

This application is a continuation-in-part of co-pending applicationSer. No. 10/795,132, filed Mar. 5, 2004, which is a continuation ofapplication Ser. No. 09/776,120, filed Feb. 2, 2001, now U.S. Pat. No.6,703,047; and is also a continuation-in-part of co-pending applicationSer. No. 10/616,055, filed Jul. 9, 2003, which is a continuation ofapplication Ser. No. 09/134,199, filed Aug. 14, 1998, now U.S. Pat. No.6,605,294. The entire disclosures of each of these references isexpressly incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates generally to apparatus and methods forsealing punctures in a body, and more particularly, to apparatus andmethods for sealing a vascular puncture extending through tissue into ablood vessel, and to apparatus and methods for delivering a plug into apercutaneous puncture extending from a patient's skin to a blood vesselor other body lumen to seal the puncture.

BACKGROUND

Apparatus and methods are known for accessing a patient's vasculaturepercutaneously, e.g., to perform a procedure within the vasculature, andfor sealing the puncture that results after completing the procedure.For example, a hollow needle may be inserted through a patient's skinand overlying tissue into a blood vessel. A guide wire may be passedthrough the needle lumen into the blood vessel, whereupon the needle maybe removed. An introducer sheath may then be advanced over the guidewire into the vessel, e.g., in conjunction with or subsequent to one ormore dilators.

A catheter or other device may be advanced through the introducer sheathand over the guide wire into a position for performing a medicalprocedure. Thus, the introducer sheath may facilitate accessing and/orintroducing various devices into the vessel, while minimizing trauma tothe vessel wall and/or minimizing blood loss. Upon completing theprocedure, the device(s) and introducer sheath may be removed, leaving apuncture extending between the skin and the vessel wall.

To seal the puncture, external pressure may be applied to the overlyingtissue, e.g., manually and/or using sandbags, until hemostasis occurs.This procedure, however, may be time consuming and expensive, requiringas much as an hour of a medical professional's time. It is alsouncomfortable for the patient, and may require the patient to remainimmobilized in the operating room, catheter lab, or holding area. Inaddition, a risk of hematoma exists from bleeding before hemostasisoccurs.

Various apparatus and methods have been suggested for sealing apercutaneous puncture instead of using external pressure. For example,U.S. Pat. No. 5,108,421 to Fowler discloses a plug that may be deliveredinto a puncture through tissue. The plug is a cylindrical rod-shapedmember which is constructed of a porous, bioabsorbable and expandablehemostatic collagen sponge or a polymerized polylactic acid orpolyglycolic acid. In one embodiment, a catheter is inserted through thepuncture into the blood vessel. A balloon on the catheter is expandedand retracted until the balloon is disposed adjacent the puncture at thewall of the vessel. The plug may be advanced into the puncture until theplug contacts the balloon. Once the plug is positioned within thepuncture, the balloon may be deflated and withdrawn, leaving the plugwithin the puncture to expand and seal the puncture and/or to promotehemostasis.

Alternatively, U.S. Pat. Nos. 5,192,302 and 5,222,974 issued to Kenseyet al. describe a bioabsorbable collagen plug that may be deliveredthrough an introducer sheath into a puncture site. The disclosed plug,however, may be difficult to position properly with respect to thevessel, which may be significant since it is generally undesirable toexpose the collagen material within the bloodstream where it may floatdownstream and cause an embolism.

U.S. Pat. No. 6,605,295 describes rods, plugs, crushed or irregularlyshaped pieces of substantially dehydrated hydrogel that may beintroduced into a lumen or void in a patient's body to seal or plug abiopsy needle track, reinforce weak tissue, or deliver a therapeuticcompound. In one embodiment, a plug of dehydrated hydrogel may bedeployed into the site of an arteriotomy and allowed to hydrate in thepresence of the tissue fluids and blood, to fill the track of thecatheter sheath and prevent further bleeding. By swelling to equilibriumhydration, the plug may lock itself firmly in place and thus reduce therisk of formation of a large hematoma at the site of the puncture.

U.S. Pat. No. 6,703,047 discloses dehydrated hydrogel precursor-based,tissue adherent compositions. The hydrogels may be used, for example,for sealing fluid leaks from tissue, as adherent drug delivery depots,and as means for augmenting and/or supporting tissue. The hydrogels maybe administered directly to an open wound site or may be dispensed,e.g., using a non-adhesive backing material, an absorbable backingmaterial, a syringe applicator, a powder atomization or aerosolizationsystem, or a needle-less injector.

SUMMARY OF THE INVENTION

The present invention is directed to apparatus and methods for sealing apuncture in a body, and, more particularly, to apparatus and methods forproviding temporary or permanent hemostasis within a vascular punctureextending into a blood vessel, and/or to apparatus and methods fordelivering a sealing plug into a percutaneous puncture extending from apatient's skin to a blood vessel or other body lumen.

In accordance with one embodiment, a device is provided for sealing apuncture extending through tissue including a carrier having apredetermined shape, e.g., a disk, cylinder, or other plug. A firsthydrogel precursor is disposed on the carrier. A second hydrogelprecursor is also disposed on the carrier. The first and second hydrogelprecursors are disposed on the carrier in an unreactive state beforeexposure to an aqueous physiological environment.

In accordance with another embodiment, an apparatus is provided forsealing a puncture extending through tissue that includes a tubularmember and a plug carried by the tubular member. The plug may includefirst and second hydrogel precursors disposed thereon, the first andsecond hydrogel precursors being in an unreactive state prior toexposure to an aqueous physiological environment in the tissue. Thedevice may include a pusher member for deploying the plug from thetubular member.

In one embodiment, the plug may include a lumen extending therethrough.The device may also include a pusher member and a positioning memberadapted to slide and/or pass through the tubular member. The positioningmember may include an elongate member and an expandable element on oneend, e.g., an expandable mesh, balloon, expandable frame, and the like,on a guidewire. In an alternative embodiment, the positioning member mayinclude a bioabsorbable foot plate or other element on one end, e.g.,for providing tactile feedback to the user during a sealing procedureand/or sealing the puncture.

In accordance with yet another embodiment, a method is provided forsealing a puncture extending through tissue and/or communicating with abody lumen. The method may include delivering a plug into a puncture,the plug including first and second hydrogel precursors disposed on acore, and a pH activating agent, the first and second hydrogelprecursors being in an unreactive state before being exposed to anaqueous physiological environment in the tissue.

In accordance with still another embodiment, a method is provided formaking a device for sealing a puncture extending through tissue. Aporous carrier and/or other core may be provided, e.g. in the shape of aplug, and first and second precursors may be applied to the core. In oneembodiment, the first and second precursors may remain in an unreactivestate until exposed to an aqueous physiological environment in thetissue. Once exposed to an aqueous physiological environment, e.g., whenexposed to fluid within a puncture, the first and second precursors mayreact with one another to create a hydrogel, an adhesive, and/or othercomposition surrounding the core that may enhance attachment of thecarrier to tissue surrounding the puncture and/or hemostasis within thepuncture.

In accordance with still another embodiment, a device is provided forsealing a puncture extending through tissue including a lyophilizedhydrogel, e.g., polyethylene glycol (PEG), or other polymer carrier. Thepolymer used in the carrier includes hydrolytically degradable chemicalgroups, thereby permitting in vivo degradation.

In one embodiment, lyophilized PEG carrier is pre-formed into a desiredshape or geometry before the lyophilization process. In anotherembodiment, the lyophilized PEG carrier is formed into the desired shapeor geometry after the lyophilization process. For example, “raw”lyophilized PEG carrier material may be shaped or otherwise modified byprocesses such as die cutting, rolling, flattening, compression molding,and the like.

In accordance with another embodiment, any of the devices describedabove may include an adherent “sticky” coating or layer disposed on anexposed surface of the polymer carrier. The adherent coating may beformed from a mixture of un-cross-linked PEG polymers and a pH adjustingagent such as, sodium borate crystals. In an exemplary process, theadherent coating mixture may be heated to melt the polymer componentsand then applied to the lyophilized PEG carrier.

In accordance with another embodiment, an apparatus is provided forsealing a puncture extending through tissue that includes a cartridgeand a plug device formed from a lyophilized PEG carrier. The plug mayinclude first and second PEG polymers disposed thereon, the first andsecond PEG polymers being in an unreactive state prior to exposure to anaqueous physiological environment in the tissue. The apparatus mayinclude a pusher member for deploying the plug from the cartridge, apositioning member, and/or an occlusion member.

In accordance with yet another embodiment, a method is provided forsealing a puncture extending through tissue and/or communicating with abody lumen. The method may include delivering a plug formed from alyophilized polymer, such as PEG or other hydrogel, into a puncture, andexposing the plug to bodily fluids, thereby causing substantialexpansion of the lyophilized material to enhance hemostasis within thepuncture. In one form, the plug may include an adherent layer formedfrom first and second PEG polymers carried in an unreactive state and/ora pH activating agent, similar to other embodiments described herein.

Other aspects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of a porous carrier in the shape of aplug.

FIG. 1B is a perspective view of the porous carrier of FIG. 1A havingfirst and second hydrogel precursors disposed thereon.

FIG. 1C is a perspective view of the porous carrier of FIG. 1B having apH activating agent disposed thereon.

FIG. 1D is a magnified cross-sectional view of the porous carrier shownin FIG. 1C, including the first and second hydrogel precursors and thepH activating agent.

FIG. 2 is a flowchart showing a method for loading two or more hydrogelprecursors on a porous carrier.

FIG. 3 is an exploded side view of an apparatus for delivering a plugdevice into a puncture through tissue.

FIGS. 4A-4F are cross-sectional views of a patient's body, showing amethod for sealing a puncture extending from the patient's skin throughintervening tissue to a body lumen.

FIGS. 5A and 5B are cross-sectional views of a patient's body, showinganother apparatus and method for sealing a puncture extending from apatient's skin through intervening tissue to a body lumen.

FIG. 6A is a perspective view of a lyophilized carrier in the shape of aplug.

FIG. 6B is a perspective view of the lyophilized carrier of FIG. 6Ahaving an adherent layer disposed thereon to provide a plug device forsealing a puncture through tissue.

FIG. 6C is a magnified cross-sectional view of the plug device of FIG.6B, showing first and second polymers and pH activating agent carried onthe plug device.

FIG. 7 is a flowchart showing a method for providing an adherent“sticky” layer on a lyophilized carrier.

FIG. 8 is an exploded side view of an apparatus for delivering a plugdevice into a puncture through tissue.

FIGS. 9A-9D are cross-sectional views of a patient's body, showing amethod for sealing a puncture extending from the patient's skin to ablood vessel using the apparatus of FIG. 8.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Turning to the drawings, FIGS. 1A-1D illustrate a device 2 for sealing apuncture extending through tissue (not shown). Generally, the device 2includes a carrier or core 4, e.g., in the shape of a plug, havingdisposed thereon a first hydrogel precursor 6 and a second hydrogelprecursor 7. The first and second hydrogel precursors 6, 7 are disposedon the carrier 4 in an unreactive state. The first and second hydrogelprecursors 6, 7 may remain in the unreactive state, e.g., before oruntil exposure to an aqueous physiological environment. An aqueousphysiological environment may exist, for example, inside a puncturetrack extending through tissue.

Blood or other bodily fluids that contact the precursor-laden carrier 4may initiate a hydrogel forming reaction between the two precursors 6,7. The reaction of the hydrogel precursors may form a cross-linkedadhesive or tacky coating that may aid in retaining the plug device 2within a puncture after deployment and/or in facilitating hemostasiswithin the puncture. Optionally, as described below, an activatingagent, e.g., a pH adjusting material 8, may also be disposed on thecarrier 4 to initiate, accelerate, or otherwise enhance the reaction ofthe precursors 6, 7.

FIG. 1A illustrates a carrier 4 in the shape of a circular cylindricalplug. It will be appreciated that the carrier 4 may have othercross-sections or shapes, such as elliptical, triangular, square,conical, disk, polygonic shapes, etc. The carrier 4 may be formed from abiocompatible and/or bioabsorbable material, for example, a porous,bioabsorbable foam or other solid material. In one embodiment, thecarrier 4 may be formed from a biocompatible and/or bioabsorbablehydrogel, e.g., polyethylene glycol (“PEG”), or other syntheticmaterial. In addition or alternatively, the carrier 4 may includepro-thrombotic material, e.g., including one or more biologicalpro-thrombotics, such as collagen, fibrin, carboxymethylcellulose,oxidized cellulose, alginates, gelatin, or other protein-based material,and/or synthetic materials, such as polyglycolic acids (PGA's),polyactides (PLA's), polyvinyl alcohol, and the like. The material ofthe carrier 4 may be at least partially absorbed by the body over time,e.g., over a period of days, weeks, or months. Optionally, the carrier 4may include therapeutic and/or pharmaceutical agents, e.g., to promotehealing, prevent infection and/or other adverse medical events, and thelike. Such agents may be embedded in the carrier material and/or appliedas one or more coatings or layers. In addition, the material of thecarrier 4 may have a substantially uniform composition or thecomposition may be varied, e.g., along its length and/or withinunderlying layers within the carrier 4.

In the embodiment shown, the carrier 4 includes a lumen 10 extendingbetween proximal and distal ends 14, 16, thereby defining a longitudinalaxis 18. The lumen 10 may be created when the carrier 4 is formed, e.g.,if the carrier 4 is rolled from one or more sheets or layers of materialor formed by molding. Alternatively, the lumen 10 may formed by boringinto or otherwise removing material from an already formed solid carrier4. The lumen 10 is dimensioned such that a guide wire or other elongatemember, such as a portion of a positioning member 40 (described in moredetail below) may slide or otherwise pass through the carrier 4, e.g.,while delivering the plug device 2.

FIG. 1B illustrates the carrier 4 loaded with first and second hydrogelprecursors 6, 7 thereon. In one embodiment, the first and secondhydrogel precursors 6, 7 are loaded onto the carrier 4 by wicking amixture of the liquid hydrogel precursors 6, 7 onto the carrier 4.Depending on the material used, the hydrogel precursors 6, 7 mayinitially be a solid dehydrated material, e.g., a powder, that may beheated above its melting point to form a liquid suitable for wicking.For example, the first and second hydrogel precursors 6, 7 may besufficiently mixed before being loaded onto the carrier 4.

Alternatively, the first and second precursor materials 6, 7 may beprovided in a liquid form into which the carrier 4 may be dipped, thatmay be poured onto the carrier 4, and/or otherwise applied to thecarrier 4 together or successively. For example, the first and secondprecursors may be dissolved in a solvent that may then be applied to thecarrier 4. In either case, once the first and second hydrogel precursors6, 7 are loaded onto the carrier 4, the first and second hydrogelprecursors 6, 7 may be in a solid or semi-solid state.

The first hydrogel precursor 6 may include any number of hydrogelprecursor materials, such as those disclosed in U.S. Pat. Nos.6,152,943, 6,165,201, 6,179,862, 6,514,534, 6,379,373, 6,703,047, and inco-pending application Ser. Nos. 10/010,715 filed Nov. 9, 2001, Ser. No.10/068,807 filed Feb. 5, 2002, and Ser. No. 10/454,362, filed Jun. 4,2003. The disclosures of these references and any others cited thereinare expressly incorporated by reference herein. For example, in oneembodiment, the first hydrogel precursor 6 may include a four arm, 10kDalton PEG with reactive ester end groups or an eight arm, 20 kDaltonPEG amine. Alternatively, the first hydrogel precursor 6 may include abioabsorbable star polymer having a complementary cross-linking speciessuch as, for example, an amino acid with reactive end groups, e.g.,lysine, dilysine, trilysine, etc.

The second hydrogel precursor 7 may include any number of hydrogelprecursor materials, e.g., a material reactive with the first precursormaterial 6 once exposed within a hydrous or aqueous environment, such asthose materials disclosed above and in the references incorporated byreference above. For example, the second precursor 7 may be the other ofan eight arm, 20 kDalton PEG amine or a four arm, 10 kDalton PEG ester.Alternatively, the second precursor 7 may be the complementarycross-linking species of a bioabsorbable star polymer, such as an aminoacid with reactive end groups, e.g., lysine, dilysine, trilysine, etc.

Referring to FIG. 1C, a pH activating agent 8 is also loaded onto thecarrier 4. The pH activating agent 8 may create a localized change in pHafter exposure to a hydrous or aqueous environment, e.g., to initiate oraccelerate the hydrogel-forming reaction. In an exemplary embodiment,the pH activating agent 8 includes solid borate crystals, such asNa₂B₄O₇.10H₂O, although different salt-based or other materials thatalter the localized pH value may be employed. Alternatively, other pHaltering agents may be used, such as sodium borate, sodium bicarbonate,and the like. In one embodiment, the pH activating agent 8 is loadedonto the carrier 4 by physically contacting solid borate crystals,powder, or other particles onto the precursor-laden (first and secondhydrogel precursors 6, 7) carrier 4. For example, the carrier 4 maysimply be rolled over a pH activating agent 8 with sufficient force toembed the pH activating agent 8 into the exterior surface 12 of thecarrier 4. Alternatively, the pH activating agent 8 may be adhered tothe exterior surface 12 of the carrier 4, e.g., by pressing particles ofthe pH activating agent 8 into the exterior surface 12, by using anadhesive (e.g., that is substantially inert or unreactive with the firstor second precursors 6, 7), and the like.

FIG. 1D illustrates a magnified cross-sectional view of the exteriorsurface 12 of the precursor-laden carrier 4 of FIG. 1D. As shown, alayer of the mixed first and second hydrogel precursors 6, 7substantially coats the exterior surface 12 of the carrier 4 in arelatively thin film or coating. Because the first and second hydrogelprecursors 6, 7 are preferably in liquid form during the wickingprocess, the first and second hydrogel precursors 6, 7 may penetrateinto the exterior surface 12 of the porous carrier 4, e.g., into poresor other recesses to substantially coat all or a significant portion ofthe carrier 4.

FIG. 1D further shows the pH activating agent 8 loaded onto the carrier4. In FIG. 1D, the pH activating agent 8 is in the form of a solid(e.g., borate crystals) with individual particles populated on top ofthe layer of first and second hydrogel precursors 6, 7. It should beunderstood, however, that the pH activating agent 8 may be loaded ontothe carrier 4 in a melted or other liquid form that remains unreactivewith the first and second hydrogel precursors 6, 7 in which case the pHactivating agent 8 may form a film, coating, or layer much like thatshown of the first and second hydrogel precursors 6, 7 in FIG. 1D.

Turning to FIG. 2, a flowchart shows an exemplary method for making asealing device, such as plug device 2 described above. First, a carrier4 is provided (step A), e.g., by forming a plug or other body from aporous, pro-thrombotic, and/or biocompatible material. As describedabove, the carrier 4 may be formed by rolling material into a desiredshape, by molding, by cutting individual devices from a larger mass ofmaterial, machining, grinding, and the like. Next, a mixture of firstand second hydrogel precursors 6, 7 is provided (step B) in apredetermined ratio, e.g., an equimolar ratio. The carrier 4 is thenloaded with first and second precursors 6, 7 (step C), which, asdescribed above, may be hydrogel precursors in liquid form. Optionally,as shown in FIG. 2, the carrier 4 may be loaded with one or moreadditional layers of hydrogel precursor material (step D). Depending onthe hydrogel employed in the plug device 2, there may be multiplehydrogel (e.g., more than two) precursors needed to initiate thehydrogel reaction. In further options, one or more therapeutic and/orpharmaceutical agents may be applied to the carrier 4, e.g., before orafter coating the carrier 4 with the first and second precursors 6, 7.

Finally, an optional pH activating agent 8 may be loaded on the carrier4 (step E). In one embodiment, the pH activating agent 8 is incrystalline or other particle form that may be physically adhered to thecarrier 4, e.g., on top of the first and second precursors 6, 7.

Turning to FIG. 3, an apparatus 1 is shown for sealing a puncturethrough tissue. Generally, the apparatus 1 may include a delivery sheathor other tubular member 20 and a plug device 2, such as those describedelsewhere herein. In addition, the apparatus 1 may include a plunger orother pusher member 30, and/or a positioning member 40.

The delivery sheath 20 may be a substantially rigid, semi-rigid, and/orflexible tubular body, including a proximal end 22, a distal end 24having a size and shape for insertion into the puncture 90, and a lumen26 extending therebetween. The distal end 24 may be tapered and/or mayinclude a substantially atraumatic tip 28 to facilitate advancementthrough a puncture. The delivery sheath 20 may include a handle (notshown), and/or one or more seals, e.g., a hemostatic seal (also notshown), on the proximal end 22. The plug device 2 may be disposed withinthe lumen 26 proximate to the distal end 24. The lumen 26 may be sizedsuch that the plug device 2 is slidable therein, e.g., able to traversedistally from the delivery sheath 20 during delivery, as describedfurther below.

The pusher member 30 may be an elongate member, e.g., a plunger,catheter, and the like, including a proximal end (not shown), and adistal end 34 having a size for slidable insertion into the lumen 26 ofthe delivery sheath 20. The distal end 34 of the pusher member 30 may besubstantially blunt to facilitate contacting, pushing, and/or “cinching”the plug device 2 within the delivery sheath 20 and/or puncture, asdescribed further below. The pusher member 30 may be substantiallyrigid, semi-rigid, and/or substantially flexible, having sufficientcolumn strength to allow movement of the delivery sheath 20 relative tothe plug device 2 without buckling the pusher member 30. The pushermember 30 may also include a lumen 36 extending between the proximal endand the distal end 34, e.g., to accommodate the positioning member 40and/or a guidewire (not shown).

In the embodiment shown in FIG. 3, the positioning member 40, e.g., aguidewire, and/or other solid or hollow elongate body, may include aproximal end 42, a distal end 44, and a positioning element 46 on thedistal end 44. The positioning element 46 may be an expandable element,such as a wire mesh structure, as shown in FIG. 3, an expandable frame46,′ as shown in FIGS. 4A-4C, and/or a balloon (not shown). Optionally,the positioning element 46 or 46′ may include a skin or other covering(not shown) on at least a proximal portion thereof, thereby making thepositioning element 46 or 46′ substantially nonporous.

The positioning element 46 or 46′ may be biased to an enlargedcondition, such as that shown in FIGS. 3 and 4A-4C, but may becompressed to a contracted condition, e.g., by an overlying sleeve orother constraint (not shown). The constraint may be removed to exposethe expandable element, allowing the expandable element to automaticallyexpand to the enlarged condition. Alternatively, the expandable elementmay be selectively expandable, e.g., using a pullwire, source ofinflation media (e.g., coupled to a lumen (not shown) extending throughthe positioning member 40 to an inflatable positioning element, notshown), or other actuator (also not shown) operable from the proximalend of the position member 40. Additional information on expandablestructures that may be incorporated into positioning member 40 may befound in U.S. Pat. Nos. 6,238,412 and 6,635,068, in co-pendingapplication Ser. No. 10/143,514, published as Publication No. US2003/0078616 A1, and Ser. No. 10/______, filed Oct. 26, 2004 andentitled “Apparatus and Methods for Delivering Sealing Materials Duringa Percutaneous Procedure to Facilitate Hemostasis” (assigned attorneymatter no. ACI-008). The entire disclosures of these references areexpressly incorporated herein by reference.

Turning to FIGS. 4A-4F, an exemplary method is shown for sealing apuncture 90 using an apparatus 1. Generally, the puncture 90 extendsfrom a patient's skin 92 through intervening tissue 96, e.g., to a bodylumen 94. In an exemplary embodiment, the puncture 90 may be apercutaneous puncture communicating with a blood vessel 94, such as afemoral artery, carotid artery, and the like.

In an exemplary method, the puncture 90 may be created using knownprocedures, e.g., using a needle, guidewire, one or more dilators, andthe like (not shown). An introducer sheath (also not shown) may beadvanced through the puncture 90 into the vessel 94, e.g., to provideaccess into the vessel 90 for one or more instruments, and/or allow oneor more diagnostic and/or interventional procedures to be performed viathe vessel 90, as is known in the art. Upon completing the procedure(s)via the vessel 94, any instruments and/or the introducer sheath (notshown) may be removed from the puncture 90.

Turning to FIG. 4A, with the positioning element 46 collapsed, thepositioning member 40 may be advanced through the puncture 90 until thepositioning element 46 is disposed within the vessel 94, whereupon thepositioning element 46 may be expanded to the enlarged condition shownin FIG. 4B. In one embodiment, the positioning member 40 may be advancedthrough a previously placed introducer sheath (not shown), e.g., beforethe introducer sheath is removed from the puncture 90. Alternatively,the positioning member 40 may be advanced directly through the puncture90 after the introducer sheath is removed.

The positioning element 46 may be maintained in the contracted condition(shown in FIG. 4A) as it is advanced through the puncture 90, e.g., byan overlying sheath or other constraint (not shown). Once thepositioning element 46 is disposed within the vessel 94, the constraintmay be removed, allowing the positioning element 46 to expandautomatically to the enlarged condition (shown in FIG. 4B).Alternatively, the positioning element 46 may be expanded to theenlarged condition via an actuator (not shown) on the proximal end 42 ofthe positioning member 40.

As shown in FIG. 4B, once the positioning element 46 is expanded, thepositioning member 40 may be partially withdrawn from the puncture 90until the positioning element 46 contacts the wall of the vessel 94, asshown in FIG. 4B. If the positioning element 46 is substantiallynonporous, the positioning element 46 may substantially seal thepuncture 90 from the vessel 94.

Turning to FIG. 4C, the apparatus 1 may be introduced into the puncture90, e.g., before or after the positioning element 46 is directed intocontact with the wall of the vessel 94. For example, the proximal end 42of the positioning member 40 may be backloaded into the distal end 24 ofthe delivery sheath 20, e.g., through the lumens 26, 10, 36 of thedelivery sheath 20, plug device 2, and pusher member 30, respectively.The delivery sheath 20 may then be advanced over the positioning member40, e.g., until the distal end 24 is disposed adjacent the vessel 94.

If the positioning element 46 has not yet been retracted, the proximalend 42 of the positioning member 40 may be pulled to draw thepositioning element 46 against the distal end 24 of the delivery sheath20 (providing a tactile feedback). The positioning member 40 may then bepulled further until the positioning element 46 contacts the wall of thevessel 94 (providing another tactile feedback), thereby partially inretracting the delivery sheath 20 back into the puncture 90.

Alternatively, if the positioning element 46 is already against the wallof the vessel 94, the delivery sheath 20 may be advanced until thedistal end 24 contacts the positioning element 46, thereby providing atactile indication that the distal end 24, and consequently the plugdevice 2, are disposed adjacent the vessel 94. If the positioningelement 46 substantially seals the puncture 90 from the vessel 94, thismay prevent or minimize blood within the vessel 94 from entering thepuncture 90, where it may seep into the lumen 26 of the delivery sheath20 and contact the plug device 2. This may be desirable to reduce anypremature reaction between the first and second precursors on the plugdevice 2.

Alternatively, the positioning member 40 may be carried initially withinthe delivery sheath 20. For example, as shown in FIGS. 5A and 5B, thepositioning member 40″ may include a foot plate 46″ on a distal end 44″thereof that may be stored within the lumen 26 of the delivery sheath 20distal to the plug device 2. As shown in FIG. 5A, the delivery sheath 20may be advanced into the puncture 90, e.g., directly or through theintroducer sheath (before its removal) with the foot plate 46″ therein.Once the distal end 24 of the delivery sheath 20 is disposed within thevessel 94, the positioning member 40″ may be advanced to expose the footplate 46″ within the vessel 94. The foot plate 46″ may changeorientation once exposed and/or may expand radially. Thereafter, thepositioning member 40″ may be partially retracted to direct the footplate 46″ into contact with the wall of the vessel 94, preventing thepositioning member 40″ from being withdrawn further. If the foot plate46″ has sufficient width, it may substantially seal the puncture 90 fromthe vessel 94.

In yet another alternative, before introducing the positioning member40, the delivery sheath 20 may be advanced into the puncture 90, e.g.,over a guidewire (not shown), which may remain after removing theintroducer sheath, through the introducer sheath (before its removal),or directly through the puncture 90. After removing any guidewire, thepositioning member 40 may be advanced into the proximal end 22 of thedelivery sheath 20 and through the lumen 10 of the plug device 2, e.g.,with the positioning element 46 in the contracted condition. The distalend 24 of the positioning member 40 may be advanced distally until thepositioning element 46 is disposed within the vessel 94. Once within thevessel 94, the positioning element 46 may be expanded and directed intocontact with the wall of the vessel 94, similar to the methods describedabove.

Turning now to FIG. 4D, the plug device 2 may then be deployed from thedelivery sheath 20. For example, as described above with respect to FIG.3, the delivery sheath 20 may include a pusher member 30 within thelumen 26 and disposed proximal to the plug device 2. With the distal end24 of the delivery sheath 20, and consequently the distal end 16 of theplug device 2, located proximal to the vessel 94, the delivery sheath 20may be retracted proximally, while maintaining the pusher member 30substantially stationary. Thus, the pusher member 30 may retain the plugdevice 2 in position within the puncture 90 while the delivery sheath 20is retracted from around the plug device 2.

In one embodiment, the plug device 2 may be offset proximally from thedistal end 24 of the delivery sheath 20 a predetermined distance, e.g.,between about two millimeters (2 mm) and ten millimeters (10 mm), and inan exemplary embodiment, about five millimeters (5 mm), such that theplug device 2 is delivered within the puncture 90 offset proximally fromthe vessel 94. Alternatively, the plug device 2 may be locatedimmediately adjacent the distal end 24 of the delivery sheath 20.

Alternatively or in addition, the pusher member 30 may be advanceddistally relative to the delivery sheath 20 to deliver the plug device 2into the puncture 90. For example, the pusher member 30 may be advanceduntil the plug device 2 abuts the positioning element 46 of thepositioning member 40. This may ensure that the plug device 2 isdelivered adjacent to the vessel 94, providing tactile feedback when theplug device 2 abuts the positioning element 46. Alternatively, as shownin FIG. 5B, if the plug device 2 is disposed within the delivery sheath20 along with the positioning element 46,″ the pusher member 30 may beused to deploy the positioning element 46″ and plug device 2sequentially.

As shown in FIG. 4E, if desired, the pusher member 30 may be used tocompress, pack, or cinch the plug device 2 within the puncture 90. Forexample, after the plug device 2 is exposed within the puncture 90(e.g., using one of the methods described above), the pusher member 30may be advanced to push the plug device 2 distally against thepositioning element 46.′ This may place the distal end 16 of the plugdevice 2 adjacent to or against the wall of the vessel 94, which mayenhance hemostasis in the arteriotomy between the vessel 94 and thepuncture 90. Optionally, the pusher member 30 may be advanced further,thereby compressing the plug device 2 axially, which may enhance theplug device 2 expanding radially to fill the puncture 90 and/or permeateoutwardly against or into the surrounding tissue.

Optionally, after the plug device 2 is deployed within the puncture 90,additional sealing compound may be delivered into the puncture 90, e.g.,to fill all or a portion of the puncture 90 above and/or around the plugdevice 2. For example, the delivery sheath 20 or the pusher member 30may be used to deliver liquid sealing compound, e.g., hydrogelprecursors (not shown), into the puncture 90, e.g., through the lumen 26(of the delivery sheath 20) or lumen 36 of the pusher member 30 (orthrough a separate lumen (not shown) in either device).

In one embodiment, the delivery sheath 20 may include one or more sideports (not shown) on the proximal end of the delivery sheath 20 that maybe coupled to a source of sealing compound, such as a syringe assemblystoring hydrogel precursors (not shown). If the delivery sheath 20 hasnot been removed entirely from the puncture 90, the delivery sheath 20may be advanced into the puncture 90 until the distal end 24 is disposedadjacent the plug device 2, whereupon the sealing compound may bedelivered into the puncture 90.

Alternatively, the delivery sheath 20 may be retracted as the sealingcompound is delivered, e.g., to at least partially fill the puncture 90.In a further alternative, e.g., if the delivery sheath 20 has beenremoved, the pusher member 30 may be used to deliver sealing compound ina similar manner to those just described. In still another alternative,a separate sheath or other delivery device (not shown) may be introducedinto the puncture 90 to deliver the liquid sealing compound above and/oraround the plug device 2. Exemplary apparatus and methods for deliveringsuch sealing compounds into the puncture 90 are disclosed in co-pendingapplications Serials Nos. 10/454,362 and 10/806,952, filed Mar. 22,2004, the entire disclosures of which are expressly incorporated byreference herein.

Turning to FIG. 4F, the positioning member 40, pusher member 30, and thedelivery sheath 20 (if the distal end 24 still extends into the puncture90) may then be removed, leaving the plug device 2 within the puncture90. The components of the apparatus 1 may be removed in any desiredorder. For example, in one method, the positioning member 40 may bewithdrawn through the plug device 2 and the lumen 36 of the pushermember 30. The pusher member 30 may restrain the plug device 2 frommoving proximally as the positioning member 40 is removed. Once thepositioning member 30 is removed, the pusher member 30 (and the deliverysheath 20, if not already removed) may then be removed.

Alternatively, the delivery sheath 20 and pusher member 30 may bewithdrawn first followed by the positioning member 40. In yet anotheralternative, the positioning element, such as the foot plate 46″ mayremain within the vessel 94 after the plug device 2 is delivered. Inthis alternative, the foot plate 46″ (or other positioning element) maybe made at least partially from a bioabsorbable material, e.g., arelatively fast absorbing material, such as that disclosed in co-pendingapplication Ser. No. 10/928,744, filed Aug. 27, 2004, entitled“Apparatus and Methods for Facilitating Hemostasis within a VascularPuncture” (attorney matter no. ACI-007), the entire disclosure of whichis expressly incorporated herein by reference.

If the positioning member 40 is removed, the positioning element 46 maybe collapsed to allow the positioning member 40 to be removed throughthe lumen 10 of the plug device 2 without substantially moving ordisrupting the plug device 2. For example, a sleeve or other constraint(not shown) may be advanced over the positioning member 40 until itcontacts and forces the positioning element 46 to collapse as it entersthe sleeve. Alternatively, if the positioning element 46 is controlledby an actuator (not shown), the actuator may be manipulated to collapsethe positioning element 46 before the positioning member 40 is removed.In another alternative, the positioning member 40 may simply be pulledproximally until the positioning element 46 contacts the plug device 2and forces the positioning element 46 to collapse as it enters the lumen10 of the plug device 2.

With the positioning element 46 collapsed, blood and/or other fluidwithin the vessel 94 may enter the puncture 90, thereby exposing theplug device 2 to an aqueous physiological environment. The aqueousphysiological environment, which may include blood or other bodilyfluids from the vessel 94 (or other body lumen) may wet the plug device2, thereby initiating a reaction between the first and second precursorsthereon. For example, the fluid may dissolve the activating agent 8,changing the pH of the fluid to initiate the first and second hydrogelprecursors 6, 8 reacting with one another. The reaction of the first andsecond hydrogel precursors 6, 7 may form an adhesive or “sticky”hydrogel coating 38 that may bond or otherwise attach to tissuesurrounding the puncture 90, which may facilitate retaining the plugdevice 2 in place within the puncture 90. In addition, the hydrogelcoating 38 may also expand or swell to further aid in retaining the plugdevice 2 within the puncture 90 and/or enhance sealing the puncture 90.It will be appreciated that, although hydrogel precursors are describedherein, other multiple component adhesives and/or reactive componentsmay be applied to the carrier 4 to create an adhesive or other coatingaround the carrier 4 when the plug device 2 is exposed to fluid withinthe patient's body.

Optionally, upon reaction of the first and second hydrogel precursors 6,7, the porous carrier 4 may be exposed to an aqueous physiologicalenvironment, e.g., blood within the puncture 90, e.g., as the first andsecond precursors 6, 8 dissolve and/or react. Thus, if the carrier 4includes pro-thrombotic material, the material may cause and/oraccelerate coagulation of the blood within the puncture 90, therebyenhancing hemostasis. Optionally, as the carrier 4 contacts blood, thecarrier 4 may expand to substantially occlude the lumen 10, althoughalternatively, the lumen 10 may be sufficiently small to seal by naturalhemostasis of the blood. In addition, if the carrier 4 includestherapeutic and/or pharmaceutical agent(s), the blood and/or surroundingtissue may become exposed to the agent(s), thereby enhancing hemostasis,patient comfort, healing, and the like.

Turning to FIGS. 6A-6C, another embodiment of a plug device 102 is shownfor sealing a puncture extending through tissue (not shown). Generally,the device 102 includes a carrier or core 104, e.g., in a predeterminedshape. The carrier 104 is formed from a lyophilized (i.e., freeze-dried)PEG polymer that contains hydrolytically degradable chemical groups.While FIGS. 6A and 6B illustrate a carrier 104 in the shape of acylindrical plug having proximal and distal ends 114, 116, it will beappreciated that the carrier 104 may have other cross-sections orshapes, such as elliptical, triangular, square, conical, disk, polygonicshapes, etc. (not shown).

In one embodiment, the carrier 104 is formed from a lyophilized PEGpolymer without any surface adherent layer or sticky coating. In thisembodiment, the carrier 104 or plug device 102 may be secured within apuncture simply due to expansion of the carrier 104 within the puncture,e.g., upon exposure to blood or other bodily fluids. The lyophilized PEGpolymer, e.g., including a macroporous polymer network, may uptake fluidand expand when exposed to an aqueous environment. The magnitude ofexpansion or swelling (pre to post hydration) may be significant, e.g.,between about two and ten times (2×-10×) its lyophilized size based onvolume. In addition or alternatively, the lyophilized hydrogel mayabsorb between about two and ten times its weight in liquid, causing thecarrier 104 to expand substantially. The hydrogel may absorb liquiduntil it is substantially saturated, e.g., within a few minutes, e.g.,not more than about two minutes.

Optionally, with additional reference to FIGS. 6B and 6C, a surfaceadherent layer or coating 106 may be provided on all or a portion of thecarrier 104. For example, the adherent layer 106 may be a mixture ofun-cross-linked PEG polymers, similar to the previous embodiments,including first and second PEG polymers 107 in an initially unreactivestate and admixed with a pH adjusting agent 108. In an exemplaryembodiment, the first PEG polymer may be formed from an amine-terminatedPEG polymer while the second PEG polymer may be formed from anester-terminated, hydrolytically degradable PEG polymer.

The first and second PEG polymers 107 may include any number of PEGpolymer precursor materials, such as those disclosed in U.S. Pat. Nos.6,152,943, 6,165,201, 6,179,862, 6,514,534, 6,379,373, 6,703,047, and inco-pending application Ser. Nos. 10/010,715 filed Nov. 9, 2001, Ser. No.10/068,807 filed Feb. 5, 2002, and Ser. No. 10/454,362, filed Jun. 4,2003, the disclosures of which are incorporated by reference above. ThepH adjusting agent 108 may include, for example, sodium borate, such asNa₂B₄O₇.10H₂O in crystalline or powder form, similar to the previousembodiments, sodium bicarbonate, or other salt-based materials, and thelike that may alter the localized pH on or around the carrier 104.

The first and second PEG polymers 107 and pH adjusting agent 108 may becarried on all or a portion of the carrier 104, e.g., dispersed on anouter surface or within the carrier 104. In particular, the first andsecond PEG polymers 107 may remain in the unreactive state, e.g., beforeor until exposure to an aqueous physiological environment, which mayexist, for example, inside a puncture or other passage through tissue.

Blood or other bodily fluids that contact the PEG polymer-laden carrier104 may initiate a cross-link forming reaction between the two PEGpolymers 107 carried in the adherent layer 106. The reaction of the PEGpolymers 107 may create a cross-linked adhesive or tacky hydrogel, whichmay aid in retaining the plug device 102 within a puncture afterdeployment and/or in facilitating hemostasis within the puncture. Thecross-linking reaction may occur, for example, when the plug device 104is in intimate contact with tissue surrounding the puncture, such as fatcells within the fascia or other tissue layers.

This cross-linking reaction may mechanically lock or otherwise securethe plug device 102 within the puncture, e.g., to maintain its positionpost-deployment. This securing property may be particularly advantageousin situations where the patient will ambulate shortly after completingthe procedure, which otherwise may increase the potential of plugmigration and, consequently, of bleeding complications. By substantiallysecuring the plug device 102 in place locally within the puncture, thetarget deployment location may be maintained within the patient whilethe puncture site heals.

In addition, the lyophilized PEG polymer forming the carrier 104 mayhydrate rapidly after contacting blood or other bodily fluids.Consequently, any blood or other bodily fluid that leaks from thepuncture site and/or surrounding tissue before significant degradationof the carrier 104 may immediately re-trigger the hydration reaction ofthe carrier 104 material, thereby improving the potential for punctureclosure.

The material of the plug device 102, i.e., the carrier 104 and/oradherent layer 106, may be at least partially absorbed by the body overtime, e.g., over a period of days, weeks, or months. Optionally, thecarrier 104 and/or adherent layer 106 may include therapeutic and/orpharmaceutical agents, e.g., to promote healing, prevent infectionand/or other adverse medical events, and the like. Such agents may beembedded in the carrier material and/or adherent layer 106 and/orapplied as one or more coatings or layers. In addition, the material ofthe carrier 104 may have a substantially uniform composition or thecomposition may be varied, e.g., along its length and/or withinunderlying layers within the carrier 104.

Returning to FIGS. 6A and 6B, in the embodiment shown, the carrier 104includes proximal and distal ends 114, 116, and a lumen 110 extendingbetween the proximal and distal ends 114, 116, thereby defining alongitudinal axis 118. The lumen 110 may be created when the carrier 104is formed, e.g., if the carrier 104 is rolled from one or more sheets orlayers of material or formed by molding. Alternatively, the lumen 110may be formed by boring into or otherwise removing material from analready formed solid carrier 104. The lumen 110 may be dimensionedand/or sized for receiving a catheter, guide wire, or other elongatemember, therethrough. For example, as described further below, a portionof a positioning member 140 may slide or otherwise pass through thelumen 110 of the carrier 104, e.g., while delivering the plug device102.

The shape of the lyophilized PEG polymer forming the carrier 104 may befixed at the time of lyophilization. Alternatively, the lyophilized PEGpolymer may be formed in various pre-formed shapes, such as sheetsand/or blocks, which may then be formed post-dehydration into a desiredgeometry, e.g., to facilitate placement within a delivery system, suchas the apparatus 101 described below. Various shaping/sizing processesmay be employed to transform the lyophilized PEG polymer into thedesired size and/or geometry, such as die cutting, rolling, flattening,compression molding, and the like.

FIG. 6B illustrates the carrier 104 loaded with a mixture of first andsecond PEG polymers 107 and a pH adjusting agent 108. In one embodiment,a powdered form of an amine-terminated polymer may be used as the firstPEG polymer while an ester terminated, hydrolytically degradable PEGpolymer in powder form is used as the second PEG polymer, similar to theprevious embodiments. Unlike the previous embodiments, the two powdersmay be mixed in a mixing container while in powder form. Powdered sodiumborate crystals, e.g., milled into a fine powder to reduce granularityand to better enable mixing, may be added to the first and second PEGpolymer 107 mixture.

The resulting mixture (first and second PEG polymers 107 and pHadjusting agent 108) may then be heated to about 40° C. to melt thefirst and second PEG polymers 107 and/or the pH adjusting agent 108. Themelted mixture is preferably thoroughly mixed, e.g., to ensure asubstantially uniform or otherwise desired distribution of theconstituents.

The melted mixture (first and second PEG polymers 107 and pH adjustingagent 108) may then be applied to all or a portion of an exposed surfaceof the carrier 104. The mixture may be applied by any number of methods,for example, by painting the heated liquid mixture onto the carrier 104with a brush or other applicator, by spraying an aerosol of the heatedliquid mixture onto the carrier 104, or by dipping or wicking the heatedliquid mixture onto the carrier 104 using a bath and the like containingthe heated liquid mixture. Once the heated liquid mixture has beensufficiently applied to the carrier 104, the mixture may be allowed tocool, e.g., to solidify and/or otherwise form the adherent layer 106.After cooling, a solid or semi-solid adherent layer 106 may surround thelyophilized carrier 102.

In one embodiment, the proximal end 114 and distal end 116 of thecarrier 104 are not covered with an adherent layer 106, as shown in FIG.6B. In this regard, the lyophilized PEG polymer at the proximal anddistal ends 114, 116 of the carrier 104 may remain exposed, e.g., tofacilitate subsequent hydration. This particular embodiment hasexcellent swelling/expansion characteristics, while substantiallymaintaining the position of the plug device 102 at a desired targetlocation.

FIG. 6C shows a magnified cross-sectional view of the exterior surfaceof the adherent layer 106 disposed on an exposed surface of alyophilized carrier 104. As shown, the first and second PEG polymers107, as well as the pH adjusting agent 108, are all well mixed withinthe entire adherent layer 106. Alternatively, the relative concentrationof the components of the adherent layer 106 may vary along the carrier104.

Turning to FIG. 7, an exemplary method is shown for making a sealingdevice, such as plug device 102 described above. First, at step A, alyophilized polymer carrier 104 is provided, e.g., by forming a plug orother body from a PEG polymer that contains hydrolytically degradablechemical groups. As described above, the carrier 104 may be formed byfolding or rolling one or more sheets of material into a desired shape,by molding, by cutting individual devices from a larger mass ofmaterial, machining, grinding, and the like.

Next, at step B, a mixture of first and second PEG polymers 107(uncross-linked) is provided in a predetermined ratio, e.g., in anequimolar ratio. Next, at step C, a pH activating agent 108, such assolid sodium borate, may be added to the mixture created in step B. Inone embodiment, the pH activating agent 108 is milled into a fine powderbefore being added to the mixture of first and second PEG polymers 107.At step D, the resulting mixture formed in step C may then be heated toa predetermined temperature to melt the first and second PEG polymers107. In one embodiment, the mixture is heated to a temperature of aboutforty degrees Celsius (40° C.). After the first and second PEG polymers107 have melted (while the borate crystals remain solid), the entiremixture may be thoroughly mixed.

At step E, the heated liquid mixture may then be applied to the carrier104, e.g., to one or more exposed surfaces of carrier 104 using one ofthe methods described above, to form the adherent layer 106. In analternative embodiment, the first and second precursors may be dissolvedin one or more solvents that allow the precursors to be mixed and/orapplied to the carrier 104, while remaining in an unreactive staterelative to one another, e.g., methylene chloride, dimethyl sulfoxide,hot acetone, and the like. Optionally, one or more therapeutic and/orpharmaceutical agents may be applied to the carrier 104 and/or adherentlayer 106. Alternatively, the adherent layer 106 may be applied orotherwise dispersed within the carrier 104, e.g., by dipping or wickingor by creating multiple layers for the carrier 104 that are coated andsuccessively formed together to create the final carrier 104.

In alternative embodiments, other laminate structures may be providedfor the plug device 102. For example, a sheet including multiple layersof different components, such as one or more of the components describedabove, may be formed, and the sheet may be rolled into a tubular orsolid cylindrical structure. An exemplary embodiment of such a sheet mayinclude three layers, e.g., a first layer of lyophilized hydrogel, asecond layer of two-part hydrogel adherent material, and a third layerof lyophilized hydrogel. Thus, in this embodiment, the adherent layer,e.g., including two hydrogel precursors in an initially unreactivestate, may be sandwiched between layers of lyophilized hydrogel.

In another embodiment, a layer of lyophilized hydrogel may be provided,and an adherent layer, e.g., including two hydrogel precursors in aninitially unreactive state, may be applied to one surface of the layerof lyophilized hydrogel. A pH adjusting agent, e.g., borate crystals,may be embedded or otherwise applied to the opposite surface of thelayer of lyophilized hydrogel. Thus, in this embodiment, the pHadjusting agent may be substantially segregated from the adherent layer.This may be desirable if to prevent the pH adjusting agent frominitiating reaction of the materials of the adherent layer prematurely,which may otherwise occur to some degree, even absent an aqueousenvironment. The resulting composite material may then be folded orrolled into a desired plug configuration.

Turning to FIGS. 8 and 9A-9D, a delivery apparatus 101 is shown forsealing a puncture 90 through tissue 96, e.g., to a vessel 94 or otherbody lumen, similar to the previous embodiments. Generally, theapparatus 101 includes an introducer or delivery sheath or other tubularmember 20 and a positioning member 140, e.g., similar to the previousembodiments. The delivery apparatus 101 also includes a cartridge 120carrying a plug device 102, such as one of those described above, and aplunger, cincher, or other pusher member 130.

The cartridge 120 generally includes an elongate tubular body includinga proximal end 122, a distal end 124, and a lumen 126 extending betweenthe proximal and distal ends 122, 124 within which the plug device 102may be carried. The pusher member 130 may also be an elongate tubularbody including a proximal end 132, a distal end 134, and a lumen 136extending between the proximal and distal ends 132, 134. The positioningmember 140 may include an elongate member having a proximal end 142, adistal end 144, and an expandable positioning element 146 on the distalend 144, such as an expandable mesh (as shown in FIG. 8), a mechanicallyexpandable structure, or a balloon (not shown).

The delivery apparatus 101 may be used to position and deliver the plugdevice 102 within a puncture 90, e.g., extravascularly just above orotherwise adjacent to the arteriotomy in a vessel 94 communicating withthe puncture 90. In one embodiment, the cartridge 120 may be insertableor otherwise slidable within lumen 26 of the delivery sheath 20, and thepusher member 130 may be slidable within the lumen 126 of the cartridge120. The plug device 102 may be compressed or otherwise disposed withinthe lumen 126 of the cartridge 120 distal to the pusher member 130. Thepositioning member 140 may insertable through the cartridge 120, e.g.,through the pusher member 130 and plug device 102.

Thus, the plug device 102 may be disposed between an inner wall of thecartridge 120 and an exterior surface of the positioning member 140. Asexplained below, the cartridge 120 may be used to shuttle the plugdevice 102 into position for deployment, i.e., through the deliverysheath 20. The pusher member 130 may be positioned proximal to the plugdevice 102 for positioning and/or maintaining the plug device 102 in apredetermined location during deployment.

With reference to FIGS. 9A-9D and 10A-10B, the delivery apparatus 101may be used to deliver the plug device 102 and/or otherwise facilitatehemostasis within a puncture 90 through tissue 94. Initially, deliverysheath 20 may be placed within the puncture 90, e.g., to provide accessto vessel 94, similar to the previous embodiments. With reference toFIG. 9A, a positioning member 140 may be introduced into and/or throughthe lumen 26 of the delivery sheath 20, e.g., with the expandable frameor other positioning element 146 thereon in a collapsed condition.

The cartridge 120 (along with the plug device 102 and pusher member 130)may be provided initially on the proximal end 142 of the positioningmember 140, as shown in FIG. 10A. Thus, the cartridge 120 may initiallybe located outside the puncture 90 as the positioning member 130 isadvanced into the puncture 90. Alternatively, the cartridge 120 may becarried on the distal end 144 of the positioning member 140, e.g., suchthat the cartridge 120 (along with the plug device 102 and pusher member130) are introduced simultaneously with the positioning member 140. In afurther alternative, the cartridge 120 may be provided separate from thepositioning member 140. When the positioning member 140 is advanced intothe puncture 90, the shaft of the positioning member 140 may extendproximally from the proximal end 22 of the delivery sheath 20, and maybe later back-loaded into the cartridge 120, e.g., through the lumen 136of the pusher member 130 and/or the lumen 110 of the plug device 102.

Still referring to FIG. 9A, the distal end 144 of the positioning member140 may be inserted through the puncture 90 and the arteriotomy into thevessel 94. The positioning element 146 on the distal end 144 of thepositioning member 140 may be expanded or otherwise deployed, similar tothe previous embodiments. As shown in FIG. 9A, the expandablepositioning element 146 on the positioning member 140 may bemechanically expanded or inflated to an enlarged condition.

After expanding the positioning element 146, the positioning member 140may be at least partially withdrawn until the positioning element 146contacts the wall of the vessel 94, e.g., to substantially seal thevessel 94 from the puncture 90. This may involve a two-step, tactileprocess, similar to the previous embodiments, in which the positioningmember 140 with expanded positioning element 146 is withdrawn until itcontacts the distal end 24 of the delivery sheath 20 and then until thepositioning element 146 contacts the wall of the vessel 94. Tension inthe proximal direction may be applied and/or maintained on thepositioning member 140 to retract the positioning element 146, e.g., toseal the puncture 90. The proximal tension may be maintained manually orusing a tensioner device (not shown), such as that disclosed inapplication Ser. No. 10/806,952 incorporated by reference above, toprovide temporary hemostasis, e.g., during the subsequent steps.

Turning to FIG. 9B, the cartridge 120 carrying the plug device 102 maybe advanced distally over the positioning member 140 into the puncture90. In one embodiment, the cartridge 120 (and plug device 102) may beadvanced through the delivery sheath 20 until a hub 123 of the cartridge120 abuts a hub 23 on the delivery sheath 20 (shown in FIG. 9C).Optionally, the positioning member 140 and/or pusher member 130 mayinclude one or more cooperating detents that may engage when thecartridge 120 reaches a predetermined location along the positioningmember 140, e.g., to limit subsequent movement of the pusher member 130relative to the positioning member 140.

For example, as shown in FIGS. 10A and 10B, the positioning member 140may include a ring, tab, or other raised element 145, and the pushermember 130 may include a living hinge, tab, or other latch element 135,e.g., on proximal end 132. For example, the latch element 135 may simplybe an annular notch in the proximal end 132 of the pusher member 130 tobias the proximal end inwardly. As the cartridge 120 (and consequentlythe pusher member 130) is advanced, the latch element 135 that may passfreely over the raised element 145. The latch element 135 then mayprevent the pusher member 130 from being retracted again, the blunt edgeof the latch element 135 abutting the ring 145 on the positioning member140.

Alternatively, the cartridge member 120 and pusher member 130 may beprovided initially on the positioning member 140, as shown in FIG. 10B.In this alternative, the pusher member 130 and positioning member 140may include the cooperating detents 133, 145 to prevent proximalmovement of the pusher member 130 relative to the positioning member140. Alternatively, the pusher member 130 may be otherwise fixedrelative to the positioning member 140, e.g., to fix the distal end 134of the pusher member 130 a predetermined distance proximal to thepositioning element 146, e.g., to position the plug device 102immediately adjacent the positioning element 146, as shown in FIG. 10B.While advanced into the delivery sheath 20 or otherwise within thepuncture 90, the plug device 102 may remain out of direct or indirectcontact with blood or other bodily fluids along the blood path.

Now referring to FIG. 9C, if the pusher member 130 is not alreadyprovided within the cartridge 120, the pusher member 130 may be advanceddistally into the lumen 126 of the cartridge 120, e.g., until a marker137 on the pusher member 130 is located adjacent to the hub 123 of thecartridge 120. As seen in FIG. 9C, this marker location may place thedistal end 134 of the pusher member 130 proximally adjacent to theproximal end 114 of the plug device 102. Alternatively, the pushermember 130 and plug device 102 may be initially positioned within thecartridge 120 as shown in FIG. 9C, i.e., with the plug device 102adjacent the distal end 124 the cartridge 120, thereby eliminating theneed to advance the pusher member 130.

Next, as shown in FIG. 9D, while proximal tension on the positioningmember 140 is used to seal the vessel 94 from the puncture 90, theposition of the pusher member 130 is maintained, and the delivery sheath20 and cartridge 120 are retracted proximally to expose or otherwisedeploy the plug device 102 within the puncture 90. The pusher member 130may serve as a stop that prevents the plug device 102 from movingproximally while the delivery sheath 20 and cartridge 120 are withdrawn.

In one embodiment, the user of the delivery apparatus 101 may positionhis or her thumb on hub 133 of the pusher member 130 to maintain itsposition while the delivery sheath 20 and cartridge 120 are retracted,e.g., using his or her index and middle fingers. For example, as shownin FIG. 9D, where the hub 123 of the cartridge 120 abuts the hub 23 ofthe delivery sheath 20, the delivery sheath 20 may be held andwithdrawn, thereby causing the cartridge 120 to be withdrawnsimultaneously. Alternatively, the cartridge 1200 may be removed first,and then the delivery sheath 120 may be removed. The cartridge 120 anddelivery sheath 20 may be removed entirely from the puncture 90 or onlyto expose the plug device 102.

Optionally, the plug device 102 may be tamped or otherwise compressedwithin the puncture 90, e.g., by advancing the pusher member 130distally to press the plug device 102 against the wall of the vessel 94and/or against the positioning element 146, similar to the previousembodiments. This may cinch the plug device 102, which may cause theplug device 102 to expand radially outwardly and/or press the plugdevice 102 against the arteriotomy, e.g., to enhance sealing thepuncture 90 from the vessel 94.

After delivering the plug device 102, the proximal tension on thepositioning member 140 may be released and/or the positioning element146 may be collapsed to its collapsed state. For example, thepositioning element 146 may be mechanically collapsed or deflated. Afterthe positioning element 146 is collapsed, the positioning member 140(and consequently the positioning element 146) may be slowly withdrawnthrough the lumen 110 of the plug 102.

In an exemplary embodiment, the positioning element 146 may have aprofile not more than about 0.875 millimeter (035 inch) to facilitateremoval of the positioning member 140 without substantially disturbingthe deployed plug device 100. While the positioning member 140 iswithdrawn, the pusher member 130 may be maintained to serve as a stopand prevent proximal migration of the plug device 102 within thepuncture 90. In addition, in embodiments where the plug device 102includes an adherent layer (not shown in FIG. 9D), the “sticky” adherentlayer may also aid in securing the plug device 102 to the surroundingtissue.

After removing the positioning member 140, the pusher member 130 may bewithdrawn, leaving the plug device 102 in place. If desired, e.g., ifbleeding occurs proximally through the lumen 136 of the pusher member130, liquid hydrogel or other sealing compound may be delivered into thepuncture 90 above and/or around the plug device 102, similar to theprevious embodiments, to assist in achieving permanent hemostasis. Forexample, a source of sealing compound (not shown) may be coupled to theproximal end 132 of the pusher member 130 and sealing compound may bedelivered into the puncture above and/or around the plug device 102.Optionally, the pusher member 130 may be retracted proximally as thesealing compound is delivered to at least partially fill the puncture 90with the sealing compound

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the scope ofthe appended claims.

1. A device for sealing a puncture extending through tissue, comprisinga carrier in a predetermined shape insertable into a puncture throughtissue, the carrier comprising lyophilized hydrogel comprisinghydrolytically degradable bonds, the hydrogel expanding when exposed toan aqueous physiological environment, the carrier having a lumenextending between proximal and distal ends thereof.
 2. The device ofclaim 1, wherein the predetermined shape comprises a disk shape, a solidcylindrical shape, a rolled sheet cylindrical shape, or a folded sheetcylindrical shape.
 3. The device of claim 1, further comprising apositioning member comprising an elongate body slidable through thelumen of the carrier and an expandable member on a distal end of theelongate body.
 4. The device of claim 1, further comprising a cartridgehaving a lumen therein, the carrier slidably disposed within thecartridge lumen.
 5. The device of claim 4, further comprising a pushermember slidable within the lumen of the cartridge for deploying thecarrier from the cartridge lumen.
 6. The device of claim 1, wherein thecarrier further comprises an adherent layer on at least a portion of anexposed surface of the carrier.
 7. The device of claim 6, whereinproximal and distal ends of the carrier do not include an adherentlayer.
 8. A device for sealing a puncture extending through tissue,comprising: a carrier comprising lyophilized hydrogel in a predeterminedshape insertable into a puncture through tissue, the hydrogel expandingwhen exposed to an aqueous physiological environment, the carriercomprising a lumen extending between proximal and distal ends thereof;and an adherent layer on at least a portion of an exposed surface of thecarrier, the adherent layer comprising a mixture of first and secondhydrogel polymers that remain in an unreactive state until exposed to anaqueous physiological environment.
 9. The device of claim 8, wherein thecarrier comprises a side wall, the adherent layer being disposed on theside wall.
 10. The device of claim 9, wherein the adherent layer isabsent from the proximal and distal ends of the carrier.
 11. The deviceof claim 8, wherein the hydrogel comprises PEG polymer.
 12. The deviceof claim 8, wherein the adherent layer further comprises a pH activatingagent.
 13. The device of claim 8, wherein the carrier comprises anelongate body having a disk shape, a solid cylindrical shape, a rolledsheet cylindrical shape, or a folded sheet cylindrical shape.
 14. Anapparatus for sealing a puncture extending through tissue, comprising: acartridge comprising a proximal end, a distal end sized for insertioninto a puncture through tissue, and a lumen extending between theproximal and distal ends; a plug slidably disposed within the cartridgelumen, the plug formed from a lyophilized hydrogel comprisinghydrolytically degradable bonds, the hydrogel expanding when exposed toan aqueous physiological environment, the plug comprising a lumenextending between proximal and distal ends thereof; and a pusher memberslidable within the cartridge lumen for deploying the plug from thecartridge.
 15. The apparatus of claim 14, the plug further comprising anadherent layer disposed on at least a portion of an exposed surfacethereof, the adherent layer comprising first and second precursorsremaining in an unreactive state until exposed to an aqueousphysiological environment.
 16. The apparatus of claim 15, wherein theadherent layer further comprises a pH adjusting agent.
 17. The apparatusof claim 15, wherein the proximal and distal ends of the carrier do notinclude an adherent layer.
 18. The apparatus of claim 14, furthercomprising a positioning member comprising an elongate member slidablethrough the lumen of the plug and an expandable occlusion elementcarried on a distal end of the elongate member.
 19. The apparatus ofclaim 14, further comprising a delivery sheath comprising a proximalend, a distal end sized for insertion into a puncture through tissue,and a lumen extending between the proximal and distal ends for receivingthe cartridge therethrough.
 20. The apparatus of claim 14, wherein theplug comprises an elongate body having a disk shape, a solid cylindricalshape, a rolled sheet cylindrical shape, or a folded sheet cylindricalshape.
 21. A method for sealing a puncture extending through tissue to abody lumen, comprising: delivering a plug comprising lyophilizedhydrogel into the puncture; and exposing the plug to bodily fluid,whereupon the lyophilized hydrogel expands to substantially seal thepuncture.
 22. The method of claim 21, wherein the lyophilized hydrogelcomprises a PEG polymer containing a hydrolytically degradable chemicalgroup.
 23. The method of claim 21, further comprising: introducing anocclusion member into the puncture until an expandable element on theocclusion member is disposed within the body lumen; expanding theexpandable element within the body lumen; and at least partiallywithdrawing the occlusion member from the puncture until the expandableelement substantially seals the body lumen from the puncture.
 24. Themethod of claim 23, wherein the plug comprises a lumen therethrough, andwherein the occlusion member is delivered into the puncture by directingthe occlusion member through the plug lumen.
 25. The method of claim 21,wherein the plug further comprises an adherent layer on at least aportion of an exposed surface thereof, the adherent layer securing theplug to tissue surrounding the puncture when exposed to bodily fluid.26. The method of claim 25, wherein the adherent layer forms a tackycoating to adhere the plug to tissue surrounding the puncture whenexposed to bodily fluid.
 27. The method of claim 25, wherein theadherent layer comprises first and second precursors that remain in anunreactive state until exposed to the bodily fluid.
 28. The method ofclaim 27, wherein the adherent layer further comprises a pH adjustingagent that modifies a local pH when the adherent layer is exposed tobodily fluid to enhance reaction of the first and second precursors. 29.The method of claim 21, wherein the plug is delivered into the puncturewithin a tubular cartridge.
 30. The method of claim 29, wherein thecartridge comprises a pusher member proximal to the plug, and whereinthe plug is delivered by retracting the cartridge while maintaining thepusher member substantially stationary to deploy the plug from thecartridge.
 31. The method of claim 30, further comprising advancing thepusher member within the puncture to compress the plug within thepuncture.
 32. The method of claim 31, further comprising deploying anocclusion element within the body lumen to substantially seal the bodylumen from the puncture, and wherein the plug is compressed between thepusher member and the occlusion element.
 33. The method of claim 21,further comprising delivering a sealing compound into the puncture afterdelivering the plug into the puncture.
 34. The method of claim 33,wherein the sealing compound comprises liquid hydrogel precursors thatflow into the puncture at least partially above or around the plug. 35.A method for sealing a puncture extending through tissue to a bodylumen, comprising: introducing a tubular sheath into the puncture untila distal end of the sheath extends into the body lumen; introducing anocclusion member into the puncture until an positioning element on theocclusion member is disposed within the body lumen; at least partiallywithdrawing the occlusion member from the puncture until the positioningelement substantially seals the body lumen from the puncture;introducing a cartridge into the puncture through the sheath, thecartridge carrying a plug therein and a pusher member proximal to theplug; at least partially withdrawing the cartridge and the sheath whilemaintaining the pusher member substantially stationary to expose theplug to bodily fluid within the puncture; advancing the pusher member tocompress the plug between the pusher member and the positioning element;and withdrawing the occlusion member and the pusher member from thepuncture, leaving the plug within the puncture adjacent the body lumen.36. The method of claim 35, further comprising delivering a sealingcompound into the puncture after delivering the plug into the puncture.37. The method of claim 36, wherein the sealing compound comprises aliquid sealant that is delivered through the pusher member into thepuncture.
 38. The method of claim 36, wherein the sealing compoundcomprises liquid hydrogel precursors that flow into the puncture atleast partially above or around the plug.
 39. The method of claim 35,wherein the plug comprises lyophilized hydrogel, the plug expanding whenexposed to bodily fluid.
 40. The method of claim 35, wherein the plugcomprises an adherent layer on at least a portion of an exposed surfacethereof, the adherent layer securing the plug to tissue surrounding thepuncture when exposed to body fluid.
 41. The method of claim 40, whereinthe adherent layer forms a tacky coating to adhere the plug to tissuesurrounding the puncture when exposed to body fluid.
 42. The method ofclaim 40, wherein the adherent layer comprises a pH adjusting agent thatmodifies a local pH when the adherent layer is exposed to body fluid toenhance reaction of the first and second precursors.
 43. The method ofclaim 35, wherein the plug comprises a lumen therethrough, and whereinthe occlusion member is delivered into the puncture by directing theocclusion member through the plug lumen.
 44. The method of claim 35,further comprising expanding the positioning element within the bodylumen before withdrawing the occlusion member.
 45. The method of claim35, wherein the occlusion member is withdrawn from the puncture beforethe pusher member is withdrawn from the puncture such that pusher memberprevents the plug from moving proximally while the occlusion member iswithdrawn.